• Title/Summary/Keyword: cyp1a1

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The clinical effects of rabeprazole sodium($Pariet^{\circledR}$) in the treatment of Layngopharyngeal Reflux (인후두역류질환 (Laryngopharyngeal Reflux Disease, LPRD)에서 Rabeprazole Sodium($Pariet^{\circledR}$)의 임상효과)

  • 최홍식;최현승;김한수
    • Korean Journal of Bronchoesophagology
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    • v.9 no.1
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    • pp.60-66
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    • 2003
  • Although there is a wide range of diseases caused by gastric acid reflux and the number of cases is on the rise, it is difficult for the laryngologist to make the correct diagnosis. The treatment for laryngopharyngeal reflux can be grouped into 3 categories - changes in lifestyle, medication, and surgery. The medication used to treat laryngopharyngeal reflux are prokinetic agents and acid supressive agents such as antacids, H2 blockers, and PPIs(Proton pump inhibitor). Rabeprazole sodium($Pariet^{\circledR}$) is a newly developed agent belonging to the PPI group, but in contrast with the existing drugs such as omeprazole, lansoprazole, pantoprazole, has a low dependency on CYP2C19 during the metabolic cycle. Thus, it is known to have a quick but fixed antiacid effect and less individual differences. We analyzed 2166 patients from 32 hospitals who were prescribed $Pariet^{\circledR}$ from May, 2001 to April, 2002. The patients were divided into 4 groups according to the duration of treatment - Group 1: 1-14 days, Group 2: 15-28 days, group 3: 29-56 days, Group 4: more than 56 days. The cases were then analyzed for improvement of 8 symptoms(heart bum, regurgitation, chronic cough, hoarseness, globus sensation, chronic throat clearing, sore throat, and dysphagia), improvement on laryngoscope, usefulness to the doctor, and complication development. Of the total of 2116 patients, 1627(75.1%) cases showed at least 50% improvement of symptoms and the amount of improvement increased according to the duration of medical treatment. Most of the patients showed objective improvement on the laryngoscope, with 32.9% showing significant improvement and 38.7% showing moderate improvement. 37.6% of the doctors questioned replied that $Pariet^{\circledR}$ was very useful and 50.3% said it was useful, showing that most were satisfied with the treatment results. The complications known to develop after taking PPI are headache, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, and of these, only a small percentage of the patients complained of mild headache. $Pariet^{\circledR}$ has shown to be a relatively safe and effective drug for the treatment of laryngopharyngeal reflux.

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EFFECT OF APF GEL ON THE SURFACE OF COMPOSITE RESIN (복합레진 표면에 대한 APF gel의 영향)

  • Yuk, Gun-Yeung;Yang, Kyu-Ho;Kim, Seon-Mi;Choi, Nam-Ki
    • Journal of the korean academy of Pediatric Dentistry
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    • v.33 no.1
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    • pp.43-52
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    • 2006
  • Topical fluoride application for children is a widely peformed procedure in the field of pediatric dentistry to prevent dental caries. However, it is recently recognized as having some unwanted effects on several esthetic restorative materials as it roughens the surface of the restorative materials. The aim of this study was to evaluate the surface changes in composite resins to topical fluoride. Composite resins(Z $250^{(R)}$, Ultraseal $XT^{(R)}$ Filtek $flow^{(R)}$ $Revolution^{(R)}$, $Denfil^{(R)}$) in topical fluoride agents were immersed and their surface roughness, weight loss and SEM were evaluated. The results were as follows : 1. The 4 minutes-immersion groups showed more roughened surface than 1 minute-immersion groups and the control groups showed the smoothest surface among all the materials, and there was statistically significant difference except the revolution between the groups. 2. There was no significant difference between the 1 minute-immersion groups and 4 minutes-immersion groups in weight loss. 3. The experimental group treated with topical fluoride gel showed the generally mere roughened surface than control group in the SEM findings.

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Combined application of rapamycin and atorvastatin improves lipid metabolism in apolipoprotein E-deficient mice with chronic kidney disease

  • Song, Eun Ju;Ahn, Sanghyun;Min, Seung-Kee;Ha, Jongwon;Oh, Goo Taeg
    • BMB Reports
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    • v.54 no.3
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    • pp.170-175
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    • 2021
  • Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA+ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA+ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

One-year experience of oral substrate reduction therapy in three patients with Gaucher disease type I

  • Sohn, Young Bae;Kim, Yewon;Moon, Ji Eun
    • Journal of Genetic Medicine
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    • v.17 no.2
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    • pp.62-67
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    • 2020
  • Purpose: Eliglustat is an oral substrate reduction therapy (SRT) approved for adults with Gaucher disease type I (GD1) who are extensive, intermediate, or poor CYP2D6 metabolizers. Here we report one-year experience of eliglustat switch therapy from long-term enzyme replacement therapy (ERT) in three adult patients with GD1. Materials and Methods: Medical history, clinical (hemoglobin concentration, platelet count, and bone mineral density) and biochemical parameters (angiotensin converting enzyme, total acid phosphatase, and lyso-gb1) of the patients were collected and evaluated by retrospective review of medical records at every 3, 6, or 12 month after switch to SRT. Results: Patient 1 was a 43-year old female diagnosed GD1 and her clinical and biochemical parameters were stabilized for more than 20 years by ERT. Due to the burden of regular hospital visit, she switched to SRT. During one-year of SRT, clinical parameters and biomarkers were maintained stable. However, after suffering acute febrile illness during SRT, she decided to re-switch to ERT due to concerns about drug interaction. Patient 2 was 41-year old male, younger brother of patient 1 and Patient 3 was 31-year old male. They switched to SRT in clinically stable condition with long-term ERT. The one-year SRT was tolerable without specific safety issue and the clinical parameters were maintained stable. Conclusion: One-year eliglustat therapy in three adult patients with GDI was generally tolerable and effective for maintaining the clinical parameters and biomarkers. However, the drug compliance, concurrent drug interactions, and long-term safety of eliglustat should be carefully monitored.

Toxicogenomic Analysis and Identification of Estrogen Responsive Genes of Di (n-ethylhexyl) Phthalate in MCF-7 Cells

  • Kim, Youn-Jung;Yun, Hye-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.149-156
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    • 2005
  • Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis

  • Wang, Mingyang;Zhao, Yan;Cao, Lingfang;Luo, Silong;Ni, Binyan;Zhang, Yi;Chen, Zeliang
    • Journal of Veterinary Science
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    • v.22 no.1
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    • pp.4.1-4.13
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    • 2021
  • Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

A case of 17 alpha-hydroxylase deficiency

  • Kim, Sung Mee;Rhee, Jeong Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.42 no.2
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    • pp.72-76
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    • 2015
  • $17{\alpha}$-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In $17{\alpha}$-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with $17{\alpha}$-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with $17{\alpha}$-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with $17{\alpha}$-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

Enhanced Nimodipine Bioavailability After Oral Administration of Nimodipine with Morin, a Flavonoid, in Rabbits

  • Choi Jun-Shik;Burm Jin-Pil
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.333-338
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    • 2006
  • The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations $(C_{max})$ of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the $C_{max}$ of nimodipine coadministered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability $(A.B\%)$ of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher $(54.1-65.0\%)$ than the control $(36.7\%)$. The increased bioavailability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

Mycelial Culture of Lentinus edodes Alleviates Rat Liver Toxicity Induced by Carbon Tetrachloride and Ethanol (표고버섯균사체의 사염화탄소 및 알콜로 처리된 흰쥐 간기능 보호 효과)

  • Ha, Yeong-L.;Kim, Young-S.;Ahn, Chae-R.;Kweon, Jung-M.;Park, Cherl-W.;Ha, Young-K.;Kim, Jeong-O.
    • Journal of Life Science
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    • v.20 no.1
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    • pp.133-141
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    • 2010
  • The protective effect of a mixed powder from solid-cultured and liquid-cultured Lentinus edodes mycelia (2:1, w/w) (designate LED) on the carbon tetrachloride ($CCl_4$)- and ethanol-induced hepatotoxicity of male Sprague-Dawley (SD) rat was investigated. In the $CCl_4$-induced rat hepatotoxicity experiment, rats of 4 groups (6 rats/group) were administere with Normal (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 200 mg/kg BW + 0.2 ml distilled water), and Silymarin (200 mg/kg BW + 0.2 ml distilled water), p.o., daily for 2 weeks. Afterwards, all groups except for the Normal group were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1:1 v/v; 0.5 ml/kg BW). For the ethanol- induced rat hepatotoxicity experiment, rats were divided into 5 groups (5 rats/group): Normal; Pair-fed control (PFC); Control (ethanol); LED (ethanol + LED 200 mg/kg BW); and Silymarin (ethanol + silymarin 200 mg/kg BW). Rats of the Normal and PFC groups were fed a basal liquid diet, and rats of the Control, LED, and Silymarin groups were fed a liquid ethanol diet containing LED or Silymarin. Eight weeks later, blood and liver samples were collected to analyze biomarkers. In $CCl_4$-induced SD rats, LED elevated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH peroxidase) activities and thiobarbituric reactive substances (TBARS) were reduced, resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities in plasma. Similar results of these enzymes and biochemical markers in both liver tissues and plasma were seen in ethanol-induced hepatotoxicity of SD rats. In addition, elevated alcohol dehydrogenase (ADH) activity and reduced expression of cytochrome p450 mixed monooxygenase enzyme (CYP2E1) were seen in liver tissues from ethanol-treated rats by LED treatment. These effects of LED were similar to those of Silymarin. In in vitro experiments, LED showed antioxidant activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) system and mouse liver mitochondria system induced by NADPH/$Fe^{2+}$ and cumine hydroperoxide (CuOOH). These results indicate that LED protected SD rat hepatotoxicity, induced by $CCl_4$ and ethanol, through its antioxidative activity and might be useful as a material for protection from hepatoxicity in humans.

Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling

  • Xiao, Yongtao;Zhou, Kejun;Lu, Ying;Yan, Weihui;Cai, Wei;Wang, Ying
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.14.1-14.14
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    • 2018
  • The link between antibiotic treatment and IF-associated liver disease (IFALD) is unclear. Here, we study the effect of antibiotic treatment on bile acid (BA) metabolism and investigate the involved mechanisms. The results showed that pediatric IF patients with cholestasis had a significantly lower abundance of BA-biotransforming bacteria than patients without cholestasis. In addition, the BA composition was altered in the serum, feces, and liver of pediatric IF patients with cholestasis, as reflected by the increased proportion of primary BAs. In the ileum, farnesoid X receptor (FXR) expression was reduced in patients with cholestasis. Correspondingly, the serum FGF19 levels decreased significantly in patients with cholestasis. In the liver, the expression of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), increased noticeably in IF patients with cholestasis. In mice, we showed that oral antibiotics (gentamicin, GM or vancomycin, VCM) reduced colonic microbial diversity, with a decrease in both Gram-negative bacteria (GM affected Eubacterium and Bacteroides) and Gram-positive bacteria (VCM affected Clostridium, Bifidobacterium and Lactobacillus). Concomitantly, treatment with GM or VCM decreased secondary BAs in the colonic contents, with a simultaneous increase in primary BAs in plasma. Moreover, the changes in the colonic BA profile especially that of tauro-beta-muricholic acid ($T{\beta}MCA$), were predominantly associated with the inhibition of the FXR and further altered BA synthesis and transport. In conclusion, the administration of antibiotics significantly decreased the intestinal microbiota diversity and subsequently altered the BA composition. The alterations in BA composition contributed to cholestasis in IF patients by regulating FXR signaling.